The present invention relates to novel compounds which are useful as sunscreens and to water resistant and long lasting sunscreen compositions.
Mammalian skin comprises two main layers; the outer cellular layer is termed the epidermis and the inner layer, which is mainly non-cellular is known as the dermis. The dermis contains structural proteins such as collagen and elastin. The outer layer of the epidermis is a non-living keratin layer known as the stratum corneum and is derived from keratinocytes of which the epidermis is mainly composed. The other types of cell in the epidermis are melanocytes which synthesise melanin and Langerhans cells which present antigens to the systemic immune system.
Solar ultra violet radiation (UVR) ranges in wavelength from about 290 nm to 400 nm. Radiation of 280 to 320 nm is known as UVB and radiation of 320 to 400 nm is termed UVA. Light of wavelength 100 to 280 nm is known as UVC.
Solar UVR is known to have various photobiological effects on the skin and these include acute effects such as erythema (sunburn) and tanning as well as longer term effects such as skin cancer and premature aging. The precise mechanisms of the reactions of sunlight on the skin are not fully understood but it seems clear that the initial event is likely to be a photochemical reaction in which a chromophore present in the skin is modified after absorption of UVR. Known chromophores in the skin include urocanic acid, which is a deamination product of histidine and is present in large quantities in the stratum corneum, nucleic acids, aromatic amino acids and melanins which are complex pigments produced by the melanocytes.
Because of the well known damaging effects of sunlight on the skin, sunscreens have been in use for many years. Sunscreens are classified by their sun protection factor against simulated solar radiation which is defined by the following equation: ##EQU1##
Until recently, most of the adverse effects of sunlight on the skin as well as tanning have been attributed to the effects of UVB but there is now an increasing body of evidence which suggests that UVA is likely to be responsible for some of the aging and carcinogenic effects of sunlight. In particular, it has been suggested that UVA could be a cause of malignant melanoma in humans (Setlow et al, Proc. Natl. Acad. Sci. 90, 6666-6670). For this reason, until relatively recently most of the sunscreens were designed only to protect from UVB and offered little or no protection from UVA. Clearly, this can be dangerous to the wearer of the sunscreen since protection from erythema caused by UVB encourages longer exposure to the sun and consequently to UVA from which the wearer of the sunscreen is not protected. It is therefore widely accepted that it is desirable for sunscreen formulations to offer protection from both UVA and UVB.
There are two conventional modes of action of sunscreens. The first of these is to prevent UVR from reaching the skin which can be done by covering the skin with a pigment which will scatter UVR. Pigments which are used in sunscreens include inorganic substances such as titanium dioxide and zinc oxide and some sunscreens also include melanin. The other strategy for providing a sunscreen is to cover the skin with a substance possessing a chromophore which absorbs light of the appropriate wavelength. Substances with suitable chromophores include anthranilates, benzophenones, camphor derivatives, cinnamates, dibenzoylmethanes, p-aminobenzoic acid (PABA) and its derivatives and salicylates. Broad spectrum protection from UVR can be achieved by combining UVA and UVB absorbing substances such as 2-ethylhexyl-4'-methoxycinnamate (.lambda.max=308 nm) and 4-.sup.t butyl-4'-methoxydibenzoylmethane (.lambda.max=355 nm).
There are, however, several problems with conventional sunscreens and one of the most serious is that they generally remain on the skin for only for a relatively short period of time. This can be dangerous as many users do not realise that their sunscreen will protect them for perhaps as little as 30 to 60 minutes when the sunlight is very intense. The problem is particularly acute for swimmers and other participants in water sports since many of the most effective sunscreens are highly soluble in water and, as water is ineffective at filtering out UVR, the user may be completely unprotected soon after entering the water. Water resistant sunscreens are available but the water resistance often arises from the way in which the compounds are formulated although water resistant sunscreens comprising a UV absorbing component attached to a polymeric backbone have also been proposed. Even with these so called water resistant sunscreens, however, it is still necessary for the user to reapply them frequently and this can be inconvenient in many water sports situations.
One approach to providing long lasting protection from UVR has been the so called "active sunscreen" formulation which includes low concentrations of the photosensitiser 5-methoxypsoralen (5-MOP) which is capable of inducing a tan which provides superior and persistent photoprotection against DNA damage. However, the use of 5-MOP has proved controversial as it photobinds to DNA and has been shown to be a photomutagen and a photocarcinogen.